Cocaine abuse and addiction has reached epidemic levels and has emerged as a national crisis. There is an urgent need to develop effective therapeutics to address this crisis. This proposal is focused on further defining the complex pharmacological elements that underlie cocaine abuse and addiction with an emphasis on expediting identification of potential therapeutics. Initially, we will compile and assemble an extensive full-rank dataset of the activity profiles of prescription and OTC drugs screened in key receptor, transport, enzyme and functional assays. This dataset will be compared to an identical activity profile of cocaine. With an internally consistent set of in vitro activity profiles and ancillary safety, drug-drug interactions, ADME pharmaco-dynamic and - kinetics information within the database, our aim is to identify combinations of existing medications and regiments potentially useful in treating cocaine abuse and addiction. We will employ this initial database as a computational "training-set" and use the results for in silico screening to illuminate new chemical entities that may be useful treating this disease. The complete dataset will be assembled into a Cocaine Profile Database which will be deployed as a technology platform for drug discovery and development related to addiction. PROPOSED COMMERCIAL APPLICATIONS: Cocaine abuse and addiction are life threatening to the abuse, disruptive to the fabric of our society and consume an estimated $50 billion each year in the U.S. in treatment costs, lost wages and other economic impacts. Successful completion of this Phase II Grant will lead to an identification of combinations of existing medications that may potentially result in therapeutics to treatment cocaine abuse and addiction. We will construct a cocaine-centered pharmacological database that will provide an information-rich, drug discovery platform useful in developing new therapeutics. We envision that this platform will become the basis for NovaScreen to establish collaborative research and development relationships with other corporations and institutions.